7-13932115-G-T

Position:

• chr7-13932115-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004956.5(ETV1):​c.555-366C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 151,572 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.024 (114 hom., cov: 32)
• Consequence: ETV1 NM_004956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

Genes affected

ETV1 (HGNC:3490): (ETS variant transcription factor 1) This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2016]

ETV1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV1	NM_004956.5	c.555-366C>A		intron_variant		ENST00000430479.6	NP_004947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV1	ENST00000430479.6	c.555-366C>A		intron_variant		1	NM_004956.5	ENSP00000405327.1
ETV1	ENST00000405358.8	c.597-366C>A		intron_variant		5		ENSP00000384085.4
ETV1	ENST00000405218.6	c.555-366C>A		intron_variant		5		ENSP00000385551.2
ETV1	ENST00000403685.5	c.501-366C>A		intron_variant		1		ENSP00000385686.1
ETV1	ENST00000403527.6	c.435-366C>A		intron_variant		1		ENSP00000384138.1
ETV1	ENST00000438956.6	c.381-366C>A		intron_variant		1		ENSP00000393078.2
ETV1	ENST00000443137.5	n.555-366C>A		intron_variant		2		ENSP00000413836.1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3611 AN: 151454 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00876

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00376

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00283

Gnomad OTH AF: 0.0168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0239 AC: 3623 AN: 151572 Hom.: 114 Cov.: 32 AF XY: 0.0228 AC XY: 1690 AN XY: 74056

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.00875

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00376

Gnomad4 FIN AF: 0.000191

Gnomad4 NFE AF: 0.00281

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.0273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17136421; hg19: chr7-13971740;